ODAC Member Raises Concerns About Dendreon's Provenge

The Cancer Letter, a weekly oncology paper (these are the guys who broke the ImClone (OTCQB:IMCL) story all those years ago, back when Inmate Waksal was spinning his lies), published an article on Dendreon (NASDAQ:DNDN) and the Advisory Panel review of Provenge. They also published a letter to the FDA from Howard Sher, a major urological oncologist from Sloan-Kettering and a member of the Oncology Drugs Advisory Committee. Dr. Scher sat on the Provenge review panel and voted against Provenge on the question of substantial efficacy.

Below are excerpts from his letter - but there's a lot more in the Cancer Letter worth reading. I think the likelihood that the FDA will not ask DNDN for additional data from the ongoing survival trial is small - though I'm confident that the trial will fail; if you are long, you might want to ask yourself if it's really worth waiting a couple of years to find out? While the CEO is selling shares? And don't forget the capital raise that is certain to be coming. May 15th we'll see a Complete Response letter from the FDA, with a request for an additional trial, and I believe the DNDN bubble will burst.

One thing is sure, from the panel vote and from this letter - even if it were to get approved, it sure doesn't look like oncologists want any part of this treatment. Maybe DNDN will have better luck selling it to the lab jockeys, PhDs and veterinarians on the advisory panel who voted for approval.

Onto Dr. Scher's words to the FDA; he's a lot more articulate and authoritative than I am:

I am writing to express concerns about the recent review of Sipuleucel-T at the FDA Advisory Meeting on March 29, 2007. These concerns are: a recommendation for approval based on data that fall short of the regulatory requirements; an inadequate statistical construct to determine definitive benefit; incomplete data on product safety; and what appear to be different criteria for approval by two Advisory Committees to the Agency. All but the latter were discussed in the open meeting, but warrant further consideration given the outcome. The concerns are based on my experience as a voting member on several ODACs representing the Agency, and separately, as a Presenter to ODAC for Industry Sponsors. I have been one of the Academic Leaders of the Prostate Cancer Clinical Trial Endpoints initiative begun under the joint Sponsorship of the FDA, AACR, ASCO and PCF in 2004, which were presented at the February 2007, Prostate ASCO Meeting in Orlando.

. . . .

Let me state at the outset that I was one of the four Committee Members who voted “no” to the question whether the trials presented by the Sponsor established the efficacy or demonstrated substantial evidence of benefit to justify an approval recommendation to the FDA. My vote was based on the fact that neither of the two trials presented met their primary endpoint, which renders the significance of results from any subsequent analyses as “exploratory” and “hypothesis generating.” As such, theresults do not constitute “proof” of benefit or justify a conclusion that they are “reasonably likely” to predict benefit. The trial data were not consistent. Even if one accepts the posthoc survival analysis results of the larger 127 patient trial (82 men treated with Sipuleucel-T and 45 men treated with a “placebo”), the second trial of 98 patients (65 treated with Sipuleucel-T and 33 with placebo) was not confirmatory. Consequently, the only conclusion that can be reached is that the survival difference observed may have occurred by chance alone, and that the results do not support an approval recommendation. This, and the Sponsor’s recognition that an additional prospective study was needed, mandates deferring any decision on whether an approval should be granted until the results of the ongoing 500 patient phase 3 trial that is powered on a primary endpoint of survival, is accrued and analyzed.

Concerns about the validity of the findings were reinforced by the absence of other signals of an antitumor effect. Specifically there were no data provided of a favorable effect on PSA, regression or stabilization of soft-tissue or boney disease radiographically, health related quality of life, or that administration of the product delayed the development of pain. Even the time to the administration of chemotherapy, an indication to the treating Physicians that the clinical course had worsened, was similar between the two groups. Reinforcing the uncertainty was the fact that in response to a direct question at the meeting, none of the Physicians representing the Sponsor could articulate how treatment with the product had “helped” any individual patient.

. . . .

Finally, the original question posed by the Agency to the Advisory Committee at the meeting was: “Does the submitted data establish the efficacy of Sipuleucel-T (APC-8015) in the intended population?” The first 4 respondees on the Committee voted “no.” The question was then changed to: Do the data show “substantial evidence.” A series of “yes” votes followed. Consider the conclusion in the manuscript describing the results of trial 9901, published in the Journal of Clinical Oncology in Volume 24, page 3093, in 2006.(JCO 24:3089, 2006) In it, the Investigators state “that while sipuleucel-T fell short of demonstrating a statistically significant difference in TTP, it MAY provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway to confirm this effect.” All of the difficulties cited, and the Investigator’s own conclusions, show how there are simply too many alternative explanations for the observed survival difference beyond treatment with Sipuleucel-T. Couple this with that fact that were no secondary signals of an antitumor effect and no confirmatory trial however flawed, mandates that any decision for approval be deferred until the phase 3 study, currently underway, has been completed and analyzed.

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